Immune checkpoint inhibitors in neoadjuvant therapy of non-small cell lung cancer: a systematic review and meta-analysis

Ge, Sa; Huang, Chenjun

doi:10.21037/jtd-21-1664

Cited by 11 publications

(13 citation statements)

References 32 publications

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“…The safety and efficacy of neoadjuvant immunotherapy for cancer treatment is an area of active research . In locally advanced esophageal cancer, the addition of immunotherapy to standard chemoradiotherapy prior to esophagectomy did not increase 30-day major complications (including readmission rate and mortality) .…”

Section: Discussionmentioning

confidence: 99%

Association of Neoadjuvant Pembrolizumab for Oral Cavity Squamous Cell Carcinoma With Adverse Events After Surgery in Treatment-Naive Patients

Tang

O’Neil

McDermott

et al. 2022

JAMA Otolaryngol Head Neck Surg

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ImportancePembrolizumab, a monoclonal antibody targeting programmed cell death 1, is currently approved by the US Food and Drug Administration for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). The potential neoadjuvant role of programmed cell death 1 inhibitors in primary surgical management of HNSCC and effects on surgical outcomes are poorly understood.ObjectiveTo evaluate the incidence of postoperative adverse events in treatment-naive patients with advanced oral cavity cancer receiving neoadjuvant pembrolizumab when compared with matched controls, as part of a window-of-opportunity multi-institutional clinical trial assessing neoadjuvant pembrolizumab for locally advanced HNSCC.Design, Setting, and ParticipantsThis retrospective cohort study at a single tertiary academic institution included treatment-naive patients with local regionally advanced oral cavity squamous cell carcinoma (OCSCC) who were undergoing surgical resection.ExposuresPatients with local regionally advanced resectable OCSCC who received neoadjuvant pembrolizumab were retrospectively reviewed for postoperative adverse events. Controls were matched by age, race, smoking status, and overall cancer stage based on historical data at the same institution. Matched-cohort analysis was performed using a McNemar test to assess differences between the groups.Main Outcomes and MeasuresIncidence of adverse events following surgical resection of advanced OCSCC within 30 days of surgery and on continued follow-up.ResultsA total of 64 patients (32 as part of the prospective clinical trial and 32 as controls; mean [SD] age, 59.6 [10.3] years; 28 [44%] women) were included in the analysis. Postoperative adverse events in the 32 patients receiving pembrolizumab included lymphedema (n = 20 [63%]), trismus (n = 7 [22%]), return to operating room (n = 7 [22%]), wound infection (n = 7 [22%]), fistula (n = 6 [19%]), wound dehiscence (n = 4 [13%]), flap failure (n = 3 [9%]), and hematoma (n = 2 [6%]). The matched control group demonstrated similar complication rates without considerable differences, except for trismus (n = 16 [50%]), which was greater by a difference of 28.1% (95% CI, 5.6%-50.6%) in the control group.Conclusions and RelevanceThis cohort study examined surgical complications among patients with local regionally advanced OCSCC treated with neoadjuvant pembrolizumab and found that serious adverse events were similar to those in patients who underwent standard-of-care treatment. This suggests that there is no increased perioperative morbidity in the use of preoperative treatment with immunotherapy. Further prospective studies are needed to validate these findings for oral cavity cancer and other subsites of the head and neck.

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Section: Discussionmentioning

confidence: 99%

Association of Neoadjuvant Pembrolizumab for Oral Cavity Squamous Cell Carcinoma With Adverse Events After Surgery in Treatment-Naive Patients

Tang

O’Neil

McDermott

et al. 2022

JAMA Otolaryngol Head Neck Surg

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“…3 Meanwhile, Ge et al conducted that neoadjuvant chemoimmunotherapy achieved more pathological relief in NSCLC but caused higher treatment-related adverse events (TRAEs) and postoperative complications than neoadjuvant immune checkpoint inhibitors (ICIs) only. 5 Neoadjuvant chemoimmunotherapy brings a new era to surgical treatment for patients with NSCLC. The neoadjuvant chemoimmunotherapy has brought efficacy and survival benefits, but the TRAEs and wound complications have still not stated clearly.…”

Section: Introductionmentioning

confidence: 99%

Analysis of treatment‐related adverse events and wound complications of surgical resection after neoadjuvant chemoimmunotherapy for non‐small cell lung cancer

Li,

Hu,

Zhang

et al. 2024

International Wound Journal

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Neoadjuvant chemoimmunotherapy is becoming an increasingly important part of the management of lung cancer to facilitate surgical resection. This study aimed to summarize the treatment‐related adverse events (TRAEs) and wound complications of neoadjuvant chemoimmunotherapy in non‐small cell lung cancer (NSCLC). Eligible studies of neoadjuvant chemoimmunotherapy for NSCLC were identified from PubMed, Embase and Web of Science. The endpoints mainly included TRAEs and wound complications. Stata18 software was used for statistical analysis with p < 0.05 considered statistically significant. Twenty studies including a total of 1072 patients were eligible for this study. Among the patients who received neoadjuvant chemoimmunotherapy, the pooled prevalence of any grade TRAEs was 77% (95% confidence interval [CI] [0.64–0.86]), grade 1–2 TRAEs was 77% (95% CI [0.58–0.89]) and grade ≥3 TRAEs was 26% (95% CI [0.16–0.38]). Surgery‐related complications rate was 22% (95% CI [0.14–0.33]). Among the wound complications, the pooled rate of air leakage was 10% (95% CI [0.04–0.23]), pulmonary/wound infection was 8% (95% CI [0.05–0.13]), bronchopleural fistula was 8% (95% CI [0.02–0.27]), bronchopulmonary haemorrhage was 3% (95% CI [0.01–0.05]), pneumonia was 5% (95% CI [0.02–0.10]), pulmonary embolism was 1% (95% CI [0.01–0.03]), pleural effusion was 7% (95% CI [0.03–0.14]) and chylothorax was 4% (95% CI [0.02–0.09]). Overall, neoadjuvant chemoimmunotherapy in NSCLC results a high incidence of grade 1–2 TRAEs but a low risk of increasing the incidence of ≥3 grade TRAEs and wound complications. These results need to be confirmed by more large‐scale prospective randomized controlled trials and studies.

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“…Neoadjuvant regimens revolutionized the treatment and increase both locoregional and systemic control, especially for immunotherapy plus chemotherapy. A meta-analysis concluded that neoadjuvant immunotherapy combined with chemotherapy achieved more pathological relief, but TRAEs and postoperative complications were also increased [ 7 ]. A meta-analysis in 2022 reported that neoadjuvant immunotherapy or chemoimmunotherapy was safe and effective in stage I–III NSCLC, and compared with neoadjuvant immunotherapy, neoadjuvant chemoimmunotherapy significantly improved the rate of pathological response without increasing SAEs or delaying surgery [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

A systematic review and meta-analysis of neoadjuvant chemoimmunotherapy in stage III non-small cell lung cancer

Liu

Zhang

et al. 2022

BMC Pulm Med

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Background Stage III non-small cell lung cancer (NSCLC) is a heterogeneous disease with different subtypes, multidisciplinary teams-led management, and a poor prognosis. Currently, the clinical benefits of stage III NSCLC in the neoadjuvant setting are still unclear. We performed a meta-analysis of published data on neoadjuvant chemoimmunotherapy in stage III NSCLC to systematically evaluate its efficacy and safety. Methods We searched the databases to identify eligible studies of neoadjuvant chemoimmunotherapy for stage III NSCLC. The primary outcomes mainly included pathological and radiological response outcomes, the feasibility of surgery, and the safety of the regimen. The pathological and radiological response included the rate of major pathologic response (MPR), complete pathologic response (pCR), radiological response outcomes, and R0 resection; The feasibility included the rate of surgical resection, conversion to thoracotomy, surgical complications, pathological downstaging of clinical disease stage. The safety included the incidence of treatment-related adverse events (TRAEs) and severe adverse events (SAEs). R 4.1.3 software was conducted for data analysis, and p < 0.05 was considered statistically significant. Results Nine trials containing a total of 382 populations were eligible for the meta-analysis, with the pooled surgical resection rate of 90%. Owing to the large heterogeneity of the single-rate meta-analysis, the random effect model was adopted. The estimated pooled prevalence of MPR was 56% (95%CI 0.39–0.72) and of pCR was 39% (95%CI 0.28–0.51). The pooled rate of TRAEs was 65% (95%CI 0.17–0.99) and SAEs was 24% (95%CI 0.05–0.49). Conclusion Compared to neoadjuvant chemotherapy or immunotherapy, neoadjuvant chemoimmunotherapy achieved more pathological and radiological relief, and has a high surgical resection rate and low risk of conversion to thoracotomy and surgical complications, with poor tolerance of toxicity but rarely developing life-threatening adverse events. In conclusion, neoadjuvant chemoimmunotherapy is suggested to be beneficial for stage III NSCLC.

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Immune checkpoint inhibitors in neoadjuvant therapy of non-small cell lung cancer: a systematic review and meta-analysis

Cited by 11 publications

References 32 publications

Association of Neoadjuvant Pembrolizumab for Oral Cavity Squamous Cell Carcinoma With Adverse Events After Surgery in Treatment-Naive Patients

Association of Neoadjuvant Pembrolizumab for Oral Cavity Squamous Cell Carcinoma With Adverse Events After Surgery in Treatment-Naive Patients

Analysis of treatment‐related adverse events and wound complications of surgical resection after neoadjuvant chemoimmunotherapy for non‐small cell lung cancer

A systematic review and meta-analysis of neoadjuvant chemoimmunotherapy in stage III non-small cell lung cancer

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